US6878341B2 - Apparatus for the precise location of reaction plates - Google Patents

Apparatus for the precise location of reaction plates Download PDF

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Publication number
US6878341B2
US6878341B2 US10/010,659 US1065901A US6878341B2 US 6878341 B2 US6878341 B2 US 6878341B2 US 1065901 A US1065901 A US 1065901A US 6878341 B2 US6878341 B2 US 6878341B2
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United States
Prior art keywords
plate
wells
support surface
wall surfaces
projection
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Expired - Fee Related, expires
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US10/010,659
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US20020094578A1 (en
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Reid Burton Kowallis
David M. Cox
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Applied Biosystems LLC
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Applera Corp
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Assigned to PE CORPORATION (NY) reassignment PE CORPORATION (NY) CROSS-REFERENCE OF CHANGE OF NAME FILED IN UNITED STATES APPLICATION N. 09/321,311, RECORDED ON MARCH 5, 2001 AT REEL NO. 011595 AND FRAME NO. 0335 Assignors: PERKIN-ELMER CORPORATION, THE
Assigned to PERKIN-ELMER CORPORATION, THE reassignment PERKIN-ELMER CORPORATION, THE CROSS-REFERENCE OF ASSIGNMENT FILED IN U.S. APPLICATION NO.O9/321311,RECORDED JULY 19,1999 AT REEL NO. O1OO96 AND FRAME NO. O923 Assignors: KOWALLIS, REID BURTON, COX, DAVID M.
Publication of US20020094578A1 publication Critical patent/US20020094578A1/en
Assigned to APPLERA CORPORATION reassignment APPLERA CORPORATION ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: PE CORPORATION (NY)
Priority to US11/069,322 priority patent/US20050152810A1/en
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Publication of US6878341B2 publication Critical patent/US6878341B2/en
Assigned to BANK OF AMERICA, N.A, AS COLLATERAL AGENT reassignment BANK OF AMERICA, N.A, AS COLLATERAL AGENT SECURITY AGREEMENT Assignors: APPLIED BIOSYSTEMS, LLC
Assigned to APPLIED BIOSYSTEMS, LLC reassignment APPLIED BIOSYSTEMS, LLC MERGER (SEE DOCUMENT FOR DETAILS). Assignors: APPLIED BIOSYSTEMS INC.
Assigned to APPLIED BIOSYSTEMS INC. reassignment APPLIED BIOSYSTEMS INC. CHANGE OF NAME (SEE DOCUMENT FOR DETAILS). Assignors: APPLERA CORPORATION
Assigned to APPLIED BIOSYSTEMS, INC. reassignment APPLIED BIOSYSTEMS, INC. LIEN RELEASE Assignors: BANK OF AMERICA, N.A.
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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/508—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
    • B01L3/5085—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1065—Multiple transfer devices
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00—Chemistry: analytical and immunological testing
    • Y10T436/11—Automated chemical analysis
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00—Chemistry: analytical and immunological testing
    • Y10T436/11—Automated chemical analysis
    • Y10T436/113332—Automated chemical analysis with conveyance of sample along a test line in a container or rack
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00—Chemistry: analytical and immunological testing
    • Y10T436/11—Automated chemical analysis
    • Y10T436/113332—Automated chemical analysis with conveyance of sample along a test line in a container or rack
    • Y10T436/114165—Automated chemical analysis with conveyance of sample along a test line in a container or rack with step of insertion or removal from test line
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00—Chemistry: analytical and immunological testing
    • Y10T436/25—Chemistry: analytical and immunological testing including sample preparation
    • Y10T436/2575—Volumetric liquid transfer

Definitions

  • the present invention relates to the positioning of multi-well plates in laboratory machines. More particularly, the invention provides an apparatus and method for accurately locating a multi-well plate at a plate-support region of a laboratory machine, so that one or more acting members, e.g., an array of pipette tips or optical readers, can operate on the individual wells.
  • one or more acting members e.g., an array of pipette tips or optical readers
  • reagent transfers e.g., aspiration and dispensing
  • mixing and stirring as well as reading the results of each assay.
  • each sample was processed in its own, separate container, such as a tube or flask, in a largely manual fashion.
  • the early methods generally provided for the processing of only one or a few samples at a time and, thus, were time consuming and labor intensive.
  • arrays of reaction wells e.g., 96 wells arranged in an 8 ⁇ 12 array formed in a tray or plate have become popular for separately performing numerous reactions at substantially the same time.
  • One aspect of the present invention provides an improvement for a microplate apparatus having (i) a tray or plate defining an array of sample wells (also referred to as a microtiter plate), (ii) a plate-handling machine having (a) a plate-support region, e g, a surface or deck, and (b) a sample-handling or reading device which operates on individual wells in the plate, and (iii) a control unit for controlling the position of the device with respect to defined coordinates (points of reference) on the plate-support surface.
  • An improved plate locating and aligning arrangement including locator structure disposed on the plate-support surface for engaging the exterior wall surfaces of one or more wells, when the plate is placed on the plate-support surface, so as to fix the position of each well at a known location with respect to the defined coordinates.
  • the locator structure includes at least one projection extending from the plate-support surface. In another embodiment, two or more projections (e.g., 2, 3 or 4) extend from the plate-support surface.
  • One or more of the projections and the exterior wall surfaces of one or more wells can be configured with complementary shaped regions.
  • the complementary shaped regions can fit closely against one another.
  • one or more of the projections taper on progressing toward their upper regions (e.g., generally having a cone shape) and one or more wells taper on progressing toward their lower regions.
  • the exterior wall surfaces of the tapered wells in this arrangement, define one or more tapered recesses, each being adapted to receive one of the tapered projections.
  • the exterior wall surfaces of four wells can define a recess into which a generally cone-shaped projection can fit.
  • each projection defines a central cavity (e.g., a hole or bore) that opens away from the plate-support surface. The cavity, in this arrangement, is configured to receive a lower region of the exterior wall surfaces of a well.
  • the locator structure includes no more than one projection for every four wells of the well array, In another embodiment, the locator structure includes no more than one projection for every six wells of the well array.
  • the locating and aligning arrangement of the invention can further include a biasing assembly operable, with a multi-well plate positioned on the plate-support surface, to urge the locator structure against regions of the exterior wall surfaces of the wells.
  • the biasing assembly includes a vacuum source and a flow line for communicating the vacuum source with a lower side of a plate, with the plate positioned on the plate-support surface.
  • the vacuum source in this embodiment, is operable to draw the plate against the plate-support surface.
  • biasing assemblies that are pneumatic, hydraulic, motorized, magnetic, and/or spring-loaded.
  • the sample-handling or reading device is attached to a support.
  • the support is adapted for movement, preferably by automated means (e.g., by way of a robotic arm or cross-bar assembly, and/or a motorized carriage directed by a control unit, or the like).
  • the movable support in this embodiment, is adapted to transport the sample-handling or reading device toward and away from a position suitable for addressing and operating on individual wells fixed at known locations with respect to the defined coordinates on the plate-support surface.
  • the sample-handling or reading device remains substantially stationary, and the plate-support surface is adapted for movement toward and away from a position whereat the device can operate on individual wells.
  • the sample-handling or reading device can include, for example, a plurality of sample-handling or reading members (also referred to herein as acting members) disposed in an array that is alignable with at least a portion of the well array, with the wells fixed at such known locations.
  • sample-handling or reading members also referred to herein as acting members
  • one or more of the acting members are pipette tips.
  • one or more of the acting members are optical sensors or readers.
  • an improved plate locating and aligning arrangement for use with a microplate apparatus, includes locator structure defined by the plate-support surface, with the locator structure being configured to engagingly receive a region of the exterior wall surfaces of at least one of the wells, when the plate is placed on the plate-support surface, so as to fix the position of each well at a known location with respect to defined coordinates on the plate-support surface.
  • the locator structure is configured to engagingly receive regions of the exterior wall surfaces of at least two wells of a multi-well plate.
  • the locator structure can include, for example, two or more cavities (e.g., holes, bores, indentations, or the like) defined by the plate-support surface, each cavity being configured to receive a lower region of the exterior wall surfaces of a respective one of the wells.
  • the locator structure comprises a cavity defined by the plate-support surface
  • a microtiter plate having wells with a non-circular horizontal cross-sectional profile.
  • the cavity has a non-circular horizontal cross-sectional profile corresponding to that of such wells.
  • both the cavity and the wells can be shaped as a triangle, square, rectangle, or other multi-sided shape; or as an oval, oblong or other rounded, but non-circular shape; or any combination thereof.
  • the locating and aligning arrangement of the invention can further include a biasing assembly operable, with a multi-well plate positioned on the plate-support surface, to urge the locator structure against regions of the exterior wall surfaces of the wells.
  • the present invention provides an improvement for a microplate apparatus having (i) a microtiter plate defining an array of sample wells, each having interior wall surfaces, (ii) a plate-handling machine having a plate-support region, e.g., a surface, and an acting-member support with one or more sample-handling or reading members disposed therealong, each member being adapted to operate on an individual well in the plate, and (iii) a control unit for controlling the position of the support with respect to defined coordinates on the plate-support surface.
  • An improved plate locating and aligning arrangement including locator structure depending from the acting-member support for engaging the interior wall surfaces of one or more wells, when introduced therein, so as to fix the position of one or more of the other wells in alignment with the sample-handling or reading member(s).
  • the locator structure and the interior wall surfaces of the wells have complementary shaped regions.
  • the complementary shaped regions can closely fit in abutment with one another.
  • the locator structure can include, for example, two or more elongate projections (e.g., each in the nature of a pin, cone, rod, or the like) disposed in spaced relation along the acting-member support.
  • the plate-handling machine includes a plurality of sample-handling or reading members (also referred to herein as acting members).
  • Such acting members and the locator structure collectively define an array that is alignable with at least a portion of the array of wells
  • two generally cone-shaped projections, each shaped for mating engagement with the interior region of one of the wells can depend from spaced apart positions along the support.
  • an array of pipette tips, optical readers, or the like can also depend from the support.
  • the projections and the acting members can define an array, such as an 8 ⁇ 12, 6 ⁇ 24, or other array.
  • the apparatus can further include a biasing assembly operable, with the locator structure inserted into one or more wells, to urge the interior wall surfaces of the wells and the locator structure together.
  • a biasing assembly operable, with the locator structure inserted into one or more wells, to urge the interior wall surfaces of the wells and the locator structure together.
  • a hydraulic, pneumatic, motorized, spring-loaded or other biasing assembly can press a support, from which the locator or other biasing assembly can press a support, from which the locator structure and acting members depend, toward the plate-support surface, with the plate interposed therebetween.
  • FIG. 1 is a partially schematic perspective view, from above, showing upwardly tapered pegs on a plate-support surface of a microplate apparatus, each peg being configured to engage exterior wall surfaces of four wells of a multi-well plate, when the plate is positioned on the surface, so as to fix the position of all of the plate's wells at known locations on the plate-support surface, thereby permitting an array of acting members to address and operate on the individual wells;
  • FIG. 2 is a top plan view showing the multi-well plate of FIG. 1 placed on the plate-support surface, with the pegs engaging the exterior wall surfaces of respective groupings of wells;
  • FIG. 3 is a partial perspective view, from above, showing one of the pegs of FIG. 2 engaging the exterior wall surfaces of a respective grouping of wells;
  • FIG. 4 is a partial top view, with portions shown in phantom, of the peg of FIG. 3 engaging the exterior wall surfaces of a respective grouping of wells;
  • FIG. 5 is a partial top view, with portions shown in phantom, showing another embodiment of a peg engaging the exterior wall surfaces of a respective grouping of wells;
  • FIG. 6 is a partial top view, with portions shown in phantom, showing still a further embodiment of a peg engaging the exterior wall surfaces of a respective grouping of wells;
  • FIG. 7 is a partial perspective view, from above, showing a projection extending from a plate-support surface, with the projection defining a cavity for engagingly receiving the exterior wall surfaces of a lower region of a well of a multi-well plate;
  • FIG. 8 is a partial perspective view, from above, showing a plurality of cavities formed in a plate-support surface, with each cavity being configured to engagingly receiving the exterior wall surfaces of a lower region of a respective well of a multi-well plate;
  • FIGS. 9A-9B are side elevational views, with portions shown in section, of a support with a pair of spaced-apart alignment projections depending therefrom, with the projections being adapted to be engagingly received within respective wells of a multi-well plate, so as to align each of a plurality of acting members, also depending from the support, with a respective well of the plate;
  • FIG. 10 is a perspective view, from below, showing a support member with a pair of spaced-apart alignment projections and ninety four acting members depending therefrom, collectively forming an 8 ⁇ 12 array, poised over a 96-well plate;
  • FIG. 11 is a perspective view, from below, showing a support member with a four alignment projections and a linear array of acting members, poised over a multi-well plate;
  • FIG. 12 is a partial perspective view, from above, showing a non-circular projection and a plurality of acting members depending from a support member, poised over a plurality of non-circular wells of a multi-well plate.
  • the present invention provides an apparatus and method for accurately locating a multi-well plate at a plate-support location, e.g., a work surface or deck, of an automated laboratory machine, such that one or more acting members, such as an array of pipette tips, optical sensors, or other members, can operate on the individual wells.
  • a plate-support location e.g., a work surface or deck
  • one or more acting members such as an array of pipette tips, optical sensors, or other members
  • features of interest of the plate such as one or more wells, are used as the primary locating structures of the plate for aligning the entire array of wells with respect to the machine.
  • the interior and/or exterior surface regions of one or more wells of a multi-well plate can be engaged by locating structure of a machine.
  • apparatus 10 includes a plate (also referred to as a tray), denoted as 12 , defining an array of sample wells, such as 14 , each having exterior wall surfaces 14 a .
  • a plate-handling machine includes (i) a plate-support region, such as surface 16 , upon which plate 12 can be placed, and (ii) a movable sample-handling or reading device, shown generally at 20 , having an array of acting members 46 (e g., reagent-transfer pins), for operating on individual wells in the plate.
  • Locator structure 22 is provided on plate-support surface 16 for quickly and accurately locating plate 12 thereon.
  • a plurality of projections 24 define the locator structure 22 , with each projection being configured as an upwardly tapered cone or peg adapted to engage the exterior wall surfaces 14 a of a respective grouping of four adjacent wells of plate 12 , when the plate is positioned on the surface (FIG. 2 ), so as to fix the position of all of the plate's wells at known locations with respect to defined coordinates, as at 26 a - 26 e , on the plate-support surface.
  • a control unit (C.U.) 28 can effect movement of the sample-handling or reading device 20 , via any suitable moving means, relative to one or more of defined coordinates 26 a - 26 e , so that individual acting members of the device can address and operate on respective wells of the plate.
  • FIGS. 3 and 4 show one upwardly tapered projection 24 , from the embodiment of FIGS. 1-2 , mated with regions of the exterior wall surfaces 14 a of a group of four downwardly tapered wells 14 of microplate 12 .
  • the projection and the wells abut along complementary shaped regions to provide a snug fit.
  • the plate is prohibited from shifting side-to-side (lateral shifting) to any significant degree across the surface. Moreover, the plate is fixed against downward (vertical) movement, relative to the surface, by (i) permitting the well bottoms to abut the work surface and/or (ii) permitting the top region of the projection to abut the lower surface of the plate.
  • each projection 24 can include a reduced-diameter, generally cylindrical or rod-like insertion portion, as at 24 a , configured to fit snugly within a respective bore or socket, such as 16 a , provided in surface 16 .
  • the projections can be held in place within the bores by any suitable means, e.g., frictional engagement, snap-fitting techniques, adhesives, fasteners, welds, etc.
  • between about 8-14 bores e.g., 12
  • All of the bores, in this embodiment are formed with substantially the same diameter and depth for receiving projections having lower regions (e.g., like region 24 a in FIG. 1 ) of a given size.
  • Two or more groups or sets of projections are provided, with the members of each group being of a selected, uniform size. Other than at their lower regions (i.e., the portions adapted to fit within a bore), the projection size differs between groups.
  • This arrangement is useful for accommodating a variety of plate types/styles. For example, a user can determine (i) which group contains projections best suited for use with a particular type of plate to be placed on the support surface (e.g., an 8 ⁇ 12 well array), and (ii) which bores on the plate support surface should receive projections from the selected group. A projection from the selected group can then be placed in each of the chosen bores. Should the user later desire to place a different type of plate on the surface (e.g., a 16 ⁇ 24 well array), a new, appropriate selection and placement of projections can be made.
  • the projections can be arranged in any suitable, desired pattern on the plate-support surface. In one embodiment, for example, several projections are clustered along a central region of the plate-support surface. In another embodiment, several projections are disposed at respective points along the perimeter of the plate-support surface. In yet a further embodiment, the projections are distributed across the plate-support surface.
  • the plate-support surface 16 and locator structures 24 are constructed to maintain a plate placed thereon, such as 12 , in a designated location for a desired length of time, even under moderate stress or pressure tending to shift or otherwise laterally displace the plate from such location, e.g., due to engagement with acting members of device 20 , or vibratory motions caused by operation of the machine.
  • each of these components is preferably formed of a substantially rigid material that resists bending, warping or other physical deformation under moderate pressure, although the material may be somewhat elastic.
  • the plate support surface is constructed of a suitable metal or metal alloy, such as stainless steel; and the locator structure 22 (e.g., each projection 24 ) is injection molded of a sturdy plastic material, such as an acrylic, polycarbonate, polypropylene, polysulfone, or the like.
  • movement of the sample-handling or reading device 20 , relative to the plate takes place in a substantially automated fashion, e.g., using any suitable moving means; although the invention can be used with manual and/or hybrid arrangements (see, e.g., U.S. Pat. No. 3,568,735; incorporated herein by reference).
  • device 20 is adapted for movement in three dimensions by way of an automated x,y,z-positioning assembly, indicated schematically at 30 , under the direction of C.U. 28 .
  • the performance envelope of positioning assembly 30 permits movement of device 20 toward, away from, and/or across (over) surface 16 , as desired.
  • Control unit 28 can be programmed, by conventional techniques, to move the device 20 to a specific location relative to one or more of the defined coordinates ( 26 a - 26 e ) on the surface.
  • positioning assembly 30 can be provided with a conventional vision system (not shown), e.g., one or more cameras or other sensing means, operatively connected to the control unit for locating coordinates on the surface.
  • a vision system e.g., one or more cameras or other sensing means, operatively connected to the control unit for locating coordinates on the surface.
  • a variety of vision systems for locating coordinate marks on a work surface are known (see, e.g., U.S. Pat. No. 5,096,353, incorporated herein by reference), and suitable systems for use herein can readily be chosen by those skilled in the art.
  • positioning assembly 30 includes a z-motion actuator coupled to an x,y-shifting assembly.
  • the z-motion actuator in this embodiment, is operatively connected to device 20 for moving it along the z direction, toward and away from a raised position.
  • the z-motion actuator can be, for example, a hydraulic, pneumatic, or motor-driven actuator.
  • the x,y-shifting assembly to which the z-motion actuator is coupled, is adapted to move the z-motion actuator linearly or in an x-y plane to locate the actuator at a selected location over the plate-support surface.
  • Exemplary automated devices useful for x,y shifting include, for example, robots with electronically controlled linked or crossed movable arms, such as a SCARA, gantry and Cartesian robots.
  • One embodiment employs a motorized x,y-carriage or rail arrangement.
  • an arm which supports the z-motion actuator is threadedly mounted on a worm screw that can be driven (rotated) in a desired direction by a stepper motor, as directed by the control unit.
  • a worm screw that can be driven (rotated) in a desired direction by a stepper motor, as directed by the control unit.
  • the plate-support surface 16 of the plate-handling machine remains substantially stationary as the sample-handling or reading device 20 is moved relative thereto. Movement of the sample-handling or reading device, however is not critical to the invention. What is required is that the position of the sample-handling or reading device be controllable with respect to defined coordinates on the plate-support surface. Providing for movement of the sample-handling or reading device is merely one way of achieving this objective. It will be appreciated that, instead of moving the sample-handling or reading device, or in addition thereto, the plate-support surface can be adapted for movement. Any such arrangements are within the scope of the present invention.
  • FIG. 1 shows device 20 as an 8 ⁇ 12 array of reagent-transfer pins depending from the lower side of a generally planar support, with each pin being adapted to pick up a selected reagent from a respective well and to transfer the reagent to a selected substrate.
  • the invention is not limited to use with such a device. Rather, the device can be of any type, and the nature of the particular device employed will generally be determined by, the application at hand Exemplary devices useful for the transfer of liquid reagents include arrays of pipettes, quills, capillary tubes, syringes jetting devices (e.g., “sip and spit” devices), etc.
  • Exemplary devices useful for transferring solid or semi-solid reagents include electrostatic and/or magnetic pins or rods, as well as vacuum capillary tubes and the like.
  • the device array can include one or more sensors and/or readers.
  • the locator structure 22 will typically include more than one such projection in order to prevent pivotal movement of the plate on the surface.
  • at least two such projections e.g., four, as shown in FIGS. 1 and 2
  • the locator structure includes no more than one projection for every four to six wells, or so, of the plate.
  • FIGS. 1-2 for example, provides only one projection for every 24 wells of the plate (i.e., four projections for a 96-well plate).
  • locator structure 22 includes a cavity that opens away from the plate support surface and in which the lower region of a respective well can be received.
  • FIG. 7 shows a cavity 324 with an axial bore 40 extending downwardly from its top region, defining the cavity for engagingly receiving the lower region of the exterior wall surfaces 14 a of a respective well 14 .
  • the cavities and wells are generally circular in horizontal cross-section, as in FIG. 7 , at least two (e.g., four) such projections/cavities are preferably provided.
  • the wells and cavities have a non-circular cross-section, on the other hand, one such cavity can be sufficient to fix the position of a plate.
  • a cavity and a mating well can be shaped as a triangle, square, rectangle, or other multi-sided shape; or as an oval, oblong or other rounded, but non-circular, shape.
  • a plurality of such non-circular cavities e.g., 2, 4 or 6 can be employed. Irrespective of each cavity's cross-sectional profile, the interior surface regions of each cavity are preferably configured to complement the exterior surface regions the wells.
  • the locator structure 22 includes one or more cavities defined by the plate-support surface itself.
  • one or more cavities e.g., holes, bores, or the like
  • each cavity being configured to engagingly receive a lower region of the exterior wall surfaces 14 a of a respective well 14 .
  • the locator structure 22 is associated with the structure supporting the acting members (e.g., pipettes, optical readers, etc.) of a machine.
  • the acting members e.g., pipettes, optical readers, etc.
  • one or more downwardly extending projections can depend from an acting-member support, along with the acting members of a machine.
  • Introduction of the projections into some of the wells of a multi-well plate serves to align the acting members with the plate's other wells.
  • the projections and the interior wall surfaces of the wells have complementary shaped regions.
  • a sample-handling or reading device 20 includes a support portion 42 operably connected to an x,y,z-positioning assembly, shown in part at 30 .
  • the locator structure in this embodiment, includes a pair of elongate projections 44 (e.g., each in the nature of a pin, cone, rod, or the like) disposed in spaced relation along support 42 .
  • any, array of acting members, such as 46 also depend from the support As the support is lowered from a position above plate 12 ( FIG. 9A ) to a position whereat each projection 44 becomes seated within a respective well 14 (FIG.
  • each projection is preferably provided with a tapered lower region to assist in bringing the plate into alignment as the support is lowered.
  • FIGS. 10-12 shows a movable support 142 having two projections 44 and ninety four acting members 46 . Together, the projections 44 and acting members 46 define an 8 ⁇ 12 array, with the projections disposed at diagonally opposed comer regions of the array. Preferably, the array is configured to be alignable with the wells of a standard 96-well plate 12 .
  • FIG. 11 shows twelve acting members 46 disposed at respective positions along a movable support 242 so as to define a linear array.
  • FIG. 12 shows a movable support 342 with a single, non-circular (square) projection 144 depending therefrom, as well as an array of acting members 46 .
  • Projection 144 is configured to fit snugly within a well 114 of plate 112 .
  • the well has a non-circular horizontal cross-section substantially like that of the projection. While only one projection is shown in FIG. 12 , it should be appreciated that additional projections can be utilized, if desired.
  • locator structure 22 of the present invention can be configured with any reasonable shape, depending upon the specific shape(s) of the mating feature on the plate.
  • any of the embodiments taught herein can further include a biasing assembly 34 operable, with a multi-well plate positioned on the plate-support surface, to urge the locator structure against the wall surfaces of the wells. This can be useful to encourage a close fit between the locator structure and such plate features. With regard to the force applied, one embodiment contemplates a delta of approximately 3 psi. For a 3′′ ⁇ 5′′ plate, for example, about 45 lbs total force is contemplated. In one embodiment, particularly useful with the arrangements of FIGS. 1-8 , the biasing assembly 34 includes a vacuum source 35 and a flow line 36 for communicating the vacuum source 35 with a lower side of a plate, with the plate positioned on the plate-support surface.
  • the vacuum source 35 is operable to draw the plate toward the plate-support surface.
  • Other embodiments contemplate, for example, biasing assemblies that are pneumatic, hydraulic, motorized, and/or spring-loaded.
  • a z-motion actuator acts as a biasing assembly 34 for pressing the plate toward the plate-support surface.
  • Positioning assembly 30 of FIGS. 9A-9B , for example, can be used to press the movable support 42 , from which the locator structure 44 and acting members 46 depend, toward the plate-support surface (upon which the plate sits), with the plate 12 interposed therebetween.
  • One embodiment contemplates, in addition to the previously described locator structure 22 , one or more walls or bumpers (not shown) disposed along the perimeter of the plate-support surface.
  • Such additional structure is preferably configured to engage the peripheral edges or sidewalls of the plate as the plate is initially being placed on the work surface, thereby effecting a gross alignment of the plate with respect to the work surface.
  • Such gross alignment can be useful for quickly positioning particular groupings of wells, e.g., those positioned about the crosses shown on the upper surface of plate 12 in FIG. 1 , over respective pegs disposed on the plate, as indicated by the drop-down dotted lines. Once grossly aligned in this fashion, the wells are then finely aligned as the exterior wall surfaces of the wells engage the pegs, as previously described.
  • the present invention can be readily adapted to accommodate microtiter plates of virtually any size and having wells disposed in any layout.
  • the particular plates used will, of course, be largely determined by the laboratory machine, or machines, and the nature of the assays (e.g., types of reagents) at hand.
  • the illustrated embodiments show arrangements configured in accordance with the popular 96-well format, the invention also contemplates any other reasonable number of wells (e.g., 12, 24, 48, 384, etc.) disposed in any suitable configuration.
  • the present invention can be used for the precise and accurate location of reaction plates on a wide variety of work surfaces, instruments and robotic manipulators.
  • work surfaces include, for example, plate-handling robots, automatic pipetters, nucleic acid (e.g., RNA or DNA) sequencers, processor work surfaces, detector stages, polymerase chain reaction (PCR) thermal cyclers, etc.
  • the invention is used with a 384-well pipettor and PE Biosystems 3700.
  • the present invention offers many advantages over the known positioning techniques. For example, the location of the reaction plates is as precise as the features of interest. Further, reaction plates made from soft or flexible material can be easily handled and accurately positioned. It will be appreciated that the present invention is adaptable to a wide variety of laboratory apparatuses, without loss of precision. Advantageously, the present invention does not require modification to existing or available reaction plates, nor attachment of any adapter(s).

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US20030228241A1 (en) * 1999-08-13 2003-12-11 Legge Coulton Heath Apparatus for liquid sample handling
US20040018615A1 (en) * 2000-08-02 2004-01-29 Garyantes Tina K. Virtual wells for use in high throughput screening assays
US20040101948A1 (en) * 2002-10-04 2004-05-27 Muser Andrew P. Multiwell plate
WO2005016527A2 (fr) * 2003-08-04 2005-02-24 Irm, Llc Transfert de fluide a base de non pression dans des systemes d'analyse de prelevement et procedes correspondants
US20070218545A1 (en) * 2006-03-17 2007-09-20 Kabushiki Kaisha Toshiba Antibody chip, antigen measuring apparatus and liquid discharging method
US20090062134A1 (en) * 2002-12-20 2009-03-05 Biotrove, Inc. Assay imaging apparatus and methods
US20100294734A1 (en) * 2005-07-22 2010-11-25 Hiroyuki Taike Samples Storage System for Pharmaceutical Development
US20110127292A1 (en) * 2009-05-25 2011-06-02 Roche Diagnostics Operations, Inc. System And Method For Dispensing Fluids
US20110300621A1 (en) * 2009-12-10 2011-12-08 Roche Molecular Systems, Inc. Process head positioning
CN102279260A (zh) * 2010-06-12 2011-12-14 北京众合百克科学仪器技术有限公司 化学发光免疫分析仪内用于夹紧酶标板的夹紧装置
US20120268904A1 (en) * 2011-04-22 2012-10-25 Hon Hai Precision Industry Co., Ltd. Flexible printed circuit board
US20130183746A1 (en) * 2012-01-17 2013-07-18 Samsung Electro-Mechanics Co., Ltd. Bio-chip module and device for measuring bio-chip
WO2014113401A1 (fr) * 2013-01-15 2014-07-24 Siemens Healthcare Diagnostics Inc. Méthodologie de positionnement de tube à automatisation
CN106248678A (zh) * 2015-06-08 2016-12-21 现代自动车株式会社 检测装置
US9778276B2 (en) 2007-11-20 2017-10-03 Hewlett-Packard Development Company, L.P. Liquid handling device

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KR20050008720A (ko) 2002-05-17 2005-01-21 벡톤 디킨슨 앤드 컴퍼니 표적 핵산 서열의 분리, 증폭 및 검출을 위한 자동화 시스템
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WO2019055033A1 (fr) * 2017-09-15 2019-03-21 Hewlett-Packard Development Company, L.P. Distribution de concentré d'adn
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US20030054543A1 (en) * 1997-06-16 2003-03-20 Lafferty William Michael Device for moving a selected station of a holding plate to a predetermined location for interaction with a probe
US20030228241A1 (en) * 1999-08-13 2003-12-11 Legge Coulton Heath Apparatus for liquid sample handling
US20040018615A1 (en) * 2000-08-02 2004-01-29 Garyantes Tina K. Virtual wells for use in high throughput screening assays
US20040101948A1 (en) * 2002-10-04 2004-05-27 Muser Andrew P. Multiwell plate
US7128878B2 (en) * 2002-10-04 2006-10-31 Becton, Dickinson And Company Multiwell plate
US20060280656A1 (en) * 2002-10-04 2006-12-14 Becton, Dickinson And Company Multiwell plate
US7410618B2 (en) 2002-10-04 2008-08-12 Becton, Dickinson And Company Multiwell plate
US20090062134A1 (en) * 2002-12-20 2009-03-05 Biotrove, Inc. Assay imaging apparatus and methods
US8697452B2 (en) * 2002-12-20 2014-04-15 Life Technologies Corporation Thermal cycling assay apparatus and method
US9428800B2 (en) 2002-12-20 2016-08-30 Life Technologies Corporation Thermal cycling apparatus and method
US20120245038A1 (en) * 2002-12-20 2012-09-27 Life Technologies Corporation Thermal cycling apparatus and method
WO2005016527A2 (fr) * 2003-08-04 2005-02-24 Irm, Llc Transfert de fluide a base de non pression dans des systemes d'analyse de prelevement et procedes correspondants
WO2005016527A3 (fr) * 2003-08-04 2006-10-12 Irm Llc Transfert de fluide a base de non pression dans des systemes d'analyse de prelevement et procedes correspondants
US20050112783A1 (en) * 2003-08-04 2005-05-26 Irm, Llc Non-pressure based fluid transfer in assay detection systems and related methods
US20100294734A1 (en) * 2005-07-22 2010-11-25 Hiroyuki Taike Samples Storage System for Pharmaceutical Development
US8349279B2 (en) * 2005-07-22 2013-01-08 Tsubakimoto Chain Co. Samples storage system for pharmaceutical development
US20070218545A1 (en) * 2006-03-17 2007-09-20 Kabushiki Kaisha Toshiba Antibody chip, antigen measuring apparatus and liquid discharging method
US9778276B2 (en) 2007-11-20 2017-10-03 Hewlett-Packard Development Company, L.P. Liquid handling device
US20110127292A1 (en) * 2009-05-25 2011-06-02 Roche Diagnostics Operations, Inc. System And Method For Dispensing Fluids
US20110300621A1 (en) * 2009-12-10 2011-12-08 Roche Molecular Systems, Inc. Process head positioning
CN102279260A (zh) * 2010-06-12 2011-12-14 北京众合百克科学仪器技术有限公司 化学发光免疫分析仪内用于夹紧酶标板的夹紧装置
US8878064B2 (en) * 2011-04-22 2014-11-04 Hong Fu Jin Precision Industry (Shenzhen) Co., Ltd. Flexible printed circuit board
US20120268904A1 (en) * 2011-04-22 2012-10-25 Hon Hai Precision Industry Co., Ltd. Flexible printed circuit board
US20130183746A1 (en) * 2012-01-17 2013-07-18 Samsung Electro-Mechanics Co., Ltd. Bio-chip module and device for measuring bio-chip
WO2014113401A1 (fr) * 2013-01-15 2014-07-24 Siemens Healthcare Diagnostics Inc. Méthodologie de positionnement de tube à automatisation
US9804181B2 (en) 2013-01-15 2017-10-31 Siemens Healthcare Diagnostics Inc. Automation tube positioning methodology
CN106248678A (zh) * 2015-06-08 2016-12-21 现代自动车株式会社 检测装置
US9982833B2 (en) * 2015-06-08 2018-05-29 Hyundai Motor Company Inspection apparatus

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CA2373741C (fr) 2006-02-07
ATE232418T1 (de) 2003-02-15
AU5164400A (en) 2000-12-18
AU754172B2 (en) 2002-11-07
US20050152810A1 (en) 2005-07-14
DE60001406T2 (de) 2004-01-15
EP1183103B1 (fr) 2003-02-12
CA2373741A1 (fr) 2000-12-07
WO2000072969A1 (fr) 2000-12-07
DE60001406D1 (de) 2003-03-20
EP1183103A1 (fr) 2002-03-06
US20020094578A1 (en) 2002-07-18
JP2003500673A (ja) 2003-01-07

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